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Hypertension and Pregnancy are accompanied by differential changes in GABAA and NMDA receptor subunit expression in the hypothalamic Paraventricular Nucleus
Author(s) -
Cork Simon,
Chazot Paul,
Pyner Susan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.891.15
Subject(s) - gabaa receptor , endocrinology , medicine , nmda receptor , gabaergic , glutamatergic , nucleus , receptor , glutamate receptor , protein subunit , chemistry , biology , neuroscience , biochemistry , gene
Sympathoexcitation is characteristic of cardiovascular disease and pregnancy. Sympathoexcitation emanates, in part, from the hypothalamic paraventricular nucleus (PVN). Hypertensive rats show that the normal balance of GABAergic inhibition and glutamatergic excitation is altered. We hypothesise that this alteration is caused by changes in the subunit composition of the GABA A and NMDA receptors in the PVN. Brains from female Wistars, female spontaneously hypertensive rats (SHR) and pregnant Wistar rats (E19) were subjected to either immunoblotting of PVN micropunches or immunohistochemistry for NMDA and GABA A receptor subunits. Expression of NMDA subunits GluN1, ‐2A and ‐2B was found in all subnuclei of the PVN. A significant increase in expression of the GluN2A subunit was observed in the PVN of SHR (P<0.05 n=3). Furthermore, a significant reduction in GABA A α1 was observed in the PVN of SHR and pregnant animals (P<0.05, n=3). A significant reduction in expression of the GABA A α5 subunits was observed in the PVN of SHR animals (P<0.001 n=3). We hypothesise that the sympathoexcitation observed in pregnancy is driven by a withdrawal in phasic GABAergic inhibition. Conversely, we believe that in SHR, the sympathoexcitation is driven by a decrease in both phasic (α1) and tonic (α5) GABA A ‐mediated inhibition, as well as an increase in NMDA‐driven excitation. Work supported by the BBSRC